Morpholine → HCID 54223004, compound

HRID 2229150Notes

Reaction equation

HRID 2229150 reaction equation
[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[CH:7][C:6]=1[CH3:19])(=[O:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[NH:72]1[CH2:77][CH2:76][O:75][CH2:74][CH2:73]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N:72]2[CH2:77][CH2:76][O:75][CH2:74][CH2:73]2)=[CH:7][C:6]=1[CH3:19])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 54194400HCID 54194400, compound

Product 1

HCID 54223004HCID 54223004, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Nitrogen was bubbled through a mixture of methyl4-(trifluoromethylsulfonyloxy)phenyl acetate (1.0 g, 3.35 mmol), cesium carbonate (1.6 g, 4.69 mmol), palladium (II) acetate (22 mg, 0.10 mmol), (S)-BINAP (93 mg, 0.15 mmol), and morpholine (0.35 mL, 4.02 mmol) in 8 mL toluene and the reaction mixture was heated to 80° C. for 6 hours. The reaction was then cooled, celite was added, and the mixture was concentrated. Chromatography was performed on a Biotage flash 40i chromatography module by loading the dried celite into a SIM and eluting with 20% ethyl acetate/hexanes (40S cartridge) providing 250 mg (37%) of the title compound as a yellow oil. 1H NMR (CDCl3; 300 MHz) δ7.19 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.3 Hz, 2H), 3.89-3.85 (m, 4H), 3.69 (s, 3H), 3.56 (s, 2H), 3.17-3.13 (m, 4H).

Workup

  1. temperatureThe reaction was then cooled
  2. additioncelite was added
  3. concentrationthe mixture was concentrated
  4. washeluting with 20% ethyl acetate/hexanes (40S cartridge)

Sources & evidence

ORD record
ord-c5bb6c7bc4894e8ab74d4c91315901de
Source dataset
uspto-grants-2002_07
Patent number
US06420349B1

Reaction notes

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